Shock index as predictor of massive transfusion and mortality in patients with trauma: a systematic review and meta-analysis

Background Management of bleeding trauma patients is still a difficult challenge. Massive transfusion (MT) requires resources to ensure the safety and timely delivery of blood products. Early prediction of MT need may be useful to shorten the time process of blood product preparation. The primary aim of this study was to assess the accuracy of shock index to predict the need for MT in adult patients with trauma. For the same population, we also assessed the accuracy of SI to predict mortality. Methods This systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. We performed a systematic search on MEDLINE, Scopus, and Web of Science from inception to March 2022. Studies were included if they reported MT or mortality with SI recorded at arrival in the field or the emergency department. The risk of bias was assessed using the QUADAS-2. Results Thirty-five studies were included in the systematic review and meta-analysis, for a total of 670,728 patients. For MT the overall sensibility was 0.68 [0.57; 0.76], the overall specificity was 0.84 [0.79; 0.88] and the AUC was 0.85 [0.81; 0.88]. Positive and Negative Likelihood Ratio (LR+; LR−) were 4.24 [3.18–5.65] and 0.39 [0.29–0.52], respectively. For mortality the overall sensibility was 0.358 [0.238; 0.498] the overall specificity 0.742 [0.656; 0.813] and the AUC 0.553 (confidence region for sensitivity given specificity: [0.4014; 0.6759]; confidence region for specificity given sensitivity: [0.4799; 0.6332]). LR+ and LR− were 1.39 [1.36–1.42] and 0.87 [0.85–0.89], respectively. Conclusions Our study demonstrated that SI may have a limited role as the sole tool to predict the need for MT in adult trauma patients. SI is not accurate to predict mortality but may have a role to identify patients with a low risk of mortality. Supplementary Information The online version contains supplementary material available at 10.1186/s13054-023-04386-w.


STUDY PROTOCOL
Study title: Shock Index as a predictor of massive transfusion in patients with trauma: a systematic review and meta-analysis.

Background
Major trauma is an important cause of death, especially in the young population. Hemorrhagic shock is the principal consequence of trauma leading to death. In the early phase of hemorrhagic shock, the organism can compensate for the blood volume loss with vasoconstriction and tachycardia. The early recognition of this condition is fundamental to trigger rapid assessment and treatment to stop hemorrhage and to trigger an appropriate transfusion therapy to rapidly replace blood loss and limit tissue hypoperfusion. Shock Index (SI) is calculated as the ratio between heart rate and systolic blood pressure and several studies showed that it is related to the severity of shock [1]. A higher value of SI was associated with the need for massive transfusion and was related to mortality [1][2][3][4]. The current European guidelines on the management of major bleeding and coagulopathy following trauma suggest using SI to assess the severity of hypovolemic shock [5]. Thus, this systematic review aims to synthesize the overall evidence about the capability of SI to predict the need for massive transfusion in patients with trauma, giving stronger evidence for its routine application in clinical practice.

Review questions and hypothesis
The primary research question is: can SI predict the need for massive transfusion in patients with trauma? We hypothesized that SI is significantly higher in trauma patients that need massive transfusion than in patients that do not need a massive transfusion. The secondary research question is: can SI predict the mortality of patients with trauma? We hypothesized that SI is significantly higher in trauma patients who do not survive after trauma than in patients that survive.

Eligibility criteria for studies
Inclusion criteria: • Studies enrolling patients with trauma • Studies reporting SI calculated in the pre-hospital setting or the Emergency Department

Primary outcome
The primary outcome of the study is to assess the accuracy of SI to detect the need for massive transfusion in patients with trauma.

Secondary outcome
The secondary outcome is to assess the accuracy of SI to detect mortality in patients with trauma.
Searches strategy MEDLINE, Scopus, and Web of Science databases will be searched electronically.
The following terms will be included: Types of study to be included Randomized controlled trials and observational trials (prospective and retrospective) will be included. Conference proceedings, abstracts, case reports, and studies not involving humans will be excluded.
No language restriction will be applied.
Selection of studies Two investigators will independently perform the first screen (title and abstract), and the full-text screen of the studies retrieved by our search. The same investigators will independently extract the data. Discrepancies at any step of the process (first screening, full-text screening, and data extraction) will be resolved by consensus or by the opinion of a third investigator.

Data extraction
The following data will be extracted from each study: • Risk of bias (quality) assessment As per the Cochrane DTA handbook [6], the QUADAS-2 tool will be used to assess for risk of bias [7]. The tool will be used by both independent reviewers, and any disagreements will be discussed with the senior author, when necessary. The overall strength and quality of the body of evidence will be assessed according to the GRADE guidelines [8,9].
Strategy for data synthesis The statistical analysis will be performed using diagmeta package in R (R version 4.2.0 (2022-04-22)), and metandi and midas in STATA (StataCorp 2021; Stata Statistical Software: Release 17; StataCorp LLC). The bivariate model proposed by Reitsma et al. will be used to assess the accuracy of SI to predict MT and mortality and for SROC calculation [4]. In case of multiple cut-offs for SI, the model of multiple thresholds proposed by Steinhuser will be used if appropriate [5].
Quantitative SROC analysis will be performed if five or more studies reported data for the primary/secondary outcome. In the presence of an appropriate number of studies, subgroup analysis considering pre-hospital SI (PH-SI) and SI recorded at hospital admission (H-SI) will be performed. Further subgroup analysis will be considered to investigate the potential sources of heterogeneity.